Subjects with Asperger's Disorder have deficits in social cognition, which may be due to abnormal brain connectivity (Belmonte, et al. 2004;Welchew, et al. 2005). Using a battery of advanced MRI techniques, we propose a study to examine anatomical and structural connectivity in a group of 40 subjects with Asperger's Disorder and 40 matched controls, focusing on limbic/paralimbic areas associated with social cognition (including the anterior and posterior cingulate, amygdala, and hippocampus). This line of research is motivated by our preliminary work showing alterations in resting-state functional connectivity networks between subjects with Asperger's Disorder and healthy controls. Our specific aims are: 1) to use functional connectivity to examine resting-state network differences;2) to use diffusion tensor imaging (DTI) to examine white matter integrity;and 3) to examine developmental effects between age groups and cohorts. This study will give us a clearer picture of the neurobiology of Asperger's Disorder, and can form the basis for extensions to Autism Spectrum Disorders (ASD). The unique capabilities and resources available to the primary investigators allow for an excellent opportunity to carry out this innovative work. PUBLIC HEALTH RELEVANCE: This project will investigate the social deficits in Asperger's Disorder using magnetic resonance imaging (MRI) to examine measures of brain connectivity. The results will further knowledge about the biological consequences of this condition, and possibly help to develop new diagnostic or therapeutic techniques.